Influenza vaccine

A vaccine is assessed by its efficacy – the extent to which it reduces risk of disease under controlled conditions – and its effectiveness – the observed reduction in risk after the vaccine is put into use.[66] In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness, which is not always caused by influenza.^[67] Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses.^[68] However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains,^[69] and even a mismatched vaccine can often provide cross-protection.^[56] The virus rapidly changes due to antigenic drift, a slight mutation in the virus that causes a new strain to arise.^[70]

The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 50–60% against

From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an intensive care unit was 82%.^[77] Effectiveness against hospitalized influenza illness in the 2019–2020 United States flu season was 41% overall and 54% in people aged 65 years or older.^[78] One review found 31% effectiveness against death among adults.^[79][80]

Repeated annual influenza vaccination generally offers consistent year-on-year protection against influenza.^[80] There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to current recommendations for yearly vaccinations but might influence future vaccination policy.^[81][82] As of 2019^[update], the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination.^[80]

There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types,^[83] but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly.^[84]

According to a 2016 study by faculty at the University of New South Wales, getting a flu shot was as effective or better at preventing a heart attack than even quitting smoking.^[85]

Children

In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that children 6 to 23 months of age be vaccinated annually against influenza.

As the death rate is also high among infants who catch influenza, the CDC and the WHO recommend that household contacts and caregivers of infants be vaccinated to reduce the risk of passing an influenza infection to the infant.[87]^[88]

In children, the vaccine appears to decrease the risk of influenza and possibly influenza-like illness.^[89] In children under the age of two data are limited.^[89] During the 2017–18 flu season, the CDC director indicated that 85 percent of the children who died "likely will not have been vaccinated".^[90]

In the United States, as of January 2019^[update], the CDC recommend that children aged six through 35 months may receive either 0.25 milliliters or 0.5 milliliters per dose of

In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of influenza vaccination in healthy 5–18-year-olds,^[94] and in 2015, published a review of the use of pediatric Fluad in children 6–72 months of age.^[95] In one study, conducted in a tertiary referral center, the rate of influenza vaccination in children was only 31%. Higher rates were found among immuno-suppressed pediatric patients (46%), and in patients with inflammatory bowel disease (50%).^[96]

Adults

In unvaccinated adults, 16% get symptoms similar to the flu, while about 10% of vaccinated adults do.^[67] Vaccination decreased confirmed cases of influenza from about 2.4% to 1.1%.^[67] No effect on hospitalization was found.^[67]

In working adults, a review by the

In health care workers, a 2006 review found a net benefit.[98] Of the eighteen studies in this review, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths.^[98] A 2014 review found benefits to patients when health care workers were immunized, as supported by moderate evidence^[99] based in part on the observed reduction in all-cause deaths in patients whose health care workers were given immunization compared with comparison patients where the workers were not offered vaccine.^[100]

Elderly

Evidence for an effect in adults over 65 is unclear.

The group most vulnerable to non-pandemic flu, the elderly, benefits least from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age.[105] In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over 65 is more than ten times more likely to die an influenza-associated death than the 50–64 age group.^[106]

There is a high-dose flu vaccine specifically formulated to provide a stronger immune response.^[107] Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine.^{[108][109][110]}

A flu vaccine containing an adjuvant was approved by the US Food and Drug Administration (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant^[111] which is an oil-in-water emulsion of squalene oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States.^{[112][113][114]} It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant.^{[115][116][117]} Per Advisory Committee on Immunization Practices guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older.^[113]

Vaccinating health care workers who work with elderly people is recommended in many countries, with the goal of reducing influenza outbreaks in this vulnerable population.

Fluad Quad was approved for use in Australia in September 2019,[122] Fluad Quadrivalent was approved for use in the United States in February 2020,^[49] and Fluad Tetra was approved for use in the European Union in May 2020.^[123][124]

Pregnancy

As well as protecting mother and child from the effects of an influenza infection, the immunization of pregnant women tends to increase their chances of experiencing a successful full-term pregnancy.^[125]

The trivalent inactivated influenza vaccine is protective in pregnant women infected with HIV.^[126]

Safety

Side effects

Common side effects of vaccination include local injection-site reactions and

While side effects of the flu vaccine may occur, they are usually minor, including soreness, redness, and swelling around the point of injection, headache, fever, nausea or fatigue.[127] Side effects of a nasal spray vaccine may include runny nose, wheezing, sore throat, cough, or vomiting.^[128]

In some people, a flu vaccine may cause serious side effects, including an allergic reaction, but this is rare. Furthermore, the common side effects and risks are mild and temporary when compared to the risks and severe health effects of the annual influenza epidemic.^[56]

Guillain–Barré syndrome

Although Guillain–Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré.^[129][130] Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates).^[131][132]

Although one review gives an incidence of about one case of Guillain–Barré per million vaccinations,^[133] a large study in China, covering close to a hundred million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain–Barré syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects.^[132][134]

Egg allergy

Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended as safe for people with egg allergies, even if severe,^[23] as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies.^[135] Studies examining the safety of influenza vaccines in people with severe egg allergies found that anaphylaxis was very rare, occurring in 1.3 cases per million doses given.^[23]

Monitoring for symptoms from vaccination is recommended in those with more severe symptoms.^[136] A study of nearly 800 children with egg allergy, including over 250 with previous anaphylactic reactions, had zero systemic allergic reactions when given the live attenuated flu vaccine.^[137][138]

Vaccines produced using other technologies, notably recombinant vaccines and those based on cell culture rather than egg protein, started to become available from 2012 in the US,^[139] and later in Europe^[140] and Australia.^[135]

Other

Several studies have identified an increased incidence of narcolepsy among recipients of the pandemic H1N1 influenza AS03-adjuvanted vaccine;^[141] efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the AS03-adjuvanted H1N1 vaccine may mimic hypocretin, serving as a trigger.^[142]

Some injection-based flu vaccines intended for adults in the United States contain

• a trivalent or quadrivalent intramuscular injection (IIV3, IIV4, or RIV4, that is, TIV or QIV), which contains the inactivated form of the virus
• a nasal spray of live attenuated influenza vaccine (LAIV, Q/LAIV), which contains the live but attenuated (weakened) form of the virus.

TIV or QIV induce protection after injection (typically intramuscular, though subcutaneous and intradermal routes can also be protective)^[147] based on an immune response to the antigens present on the inactivated virus, while cold-adapted LAIV works by establishing infection in the nasal passages.^[148]

Recommendations

Various public health organizations, including the World Health Organization (WHO), recommend that yearly influenza vaccination be routinely offered, particularly to people at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including:

• people aged 50 years of age or older^[19]
• people with chronic lung diseases, including asthma^[19]
• people with chronic heart diseases^[19]
• people with chronic liver diseases^[19]
• people with chronic kidney diseases^[19]
• people who have had their spleen removed or whose spleen is not working properly^{[medical citation needed]}
• people who are immunocompromised^[19]
• residents of nursing homes and other long-term care facilities^[19]
• health care workers (both to prevent sickness and to prevent spread to their patients)^[149][150]
• women who are or will be pregnant during the influenza season^[19]
• children and adolescents (aged 6 months through 18 years) who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection^[19]
• American Indians/Alaska Natives^[19]
• people who are extremely obese (body mass index ≥40 for adults)^[19]

The flu vaccine is contraindicated for those under six months of age and those with severe, life-threatening allergies to flu vaccine or any ingredient in the vaccine.^{[17][151][23]}

World Health Organization

As of 2016^[update], the World Health Organization (WHO) recommends seasonal influenza vaccination for:^{[152][153][154][155][156]}

First priority:

• Pregnant women

Second priority (in no particular order):

• Children aged 6–59 months
• Elderly
• Individuals with specific chronic medical conditions
• Health-care workers

Canada

The National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada, recommends that everyone over six months of age be encouraged to receive annual influenza vaccination, and that children between the age of six months and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.^[157] Particularly:

• People at high risk of influenza-related complications or hospitalization, including people who are morbidly obese, healthy pregnant women, children aged 6–59 months, the elderly, aboriginals, and people with one of an itemized list of chronic health conditions
• People capable of transmitting influenza to those at high risk, including household contacts and health care workers
• People who provide essential community services
• Certain poultry workers

Live attenuated influenza vaccine (LAIV) was not available in Canada for the 2019–2020 season.^[157]

European Union

The European Centre for Disease Prevention and Control (ECDC) recommends vaccinating the elderly as a priority, with a secondary priority people with chronic medical conditions and health care workers.^[158]

The influenza vaccination strategy is generally that of protecting vulnerable people, rather than limiting influenza circulation or eliminating human influenza sickness. This is in contrast with the high herd immunity strategies for other infectious diseases such as polio and measles.^[159] This is also due in part to the financial and logistics burden associated with the need of an annual injection.^[160]

United States

In the United States routine influenza vaccination is recommended for all persons aged six months and over.^[19][161] It takes up to two weeks after vaccination for sufficient antibodies to develop in the body.^[161] The CDC recommends vaccination before the end of October,^[19] although it considers getting a vaccine in December or even later to be still beneficial.^{[19][56][161]} The U.S. military also requires a flu shot annually for its active and reserve servicemembers.^[162]

According to the CDC, the live attenuated virus (LAIV4) (which comes in the form of the nasal spray in the US) should be avoided by some groups.^[19][163]

Within its blanket recommendation for general vaccination in the United States, the CDC, which began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their

Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications.^[164] In 2009, a new high-dose formulation of the standard influenza vaccine was approved.^[165] The Fluzone High Dose is specifically for people 65 and older; the difference is that it has four times the antigen dose of the standard Fluzone.^{[166][167][168][169]}

The US government requires hospitals to report worker vaccination rates. Some US states and hundreds of US hospitals require health care workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow collective bargaining grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks.^[170]

Vaccination against influenza is especially considered important for members of high-risk groups who would be likely to have complications from influenza, for example pregnant women^[19][171] and children and teenagers from six months to 18 years of age who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection;^[19]

• In raising the upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications^[172]
• An added benefit expected from the vaccination of children is a reduction in the number of influenza cases among parents and other household members, and of possible spread to the general community.^[172]

The CDC indicated that live attenuated influenza vaccine (LAIV), also called the nasal spray vaccine, was not recommended for the 2016–2017 flu season in the United States.^[173]

Furthermore, the CDC recommends that health care personnel who care for severely immunocompromised persons receive injections (TIV or QIV) rather than LAIV.^[174]

Australia

The Australian Government recommends seasonal flu vaccination for everyone over the age of six months. Australia uses inactivated vaccines.^[175] Until 2021, the egg-based vaccine has been the only one available (and continues to be the only free one), but from March 2021 a new cell-based vaccine is available for those who wish to pay for it, and it is expected that this one will become the standard by 2026.^[135] The standard flu vaccine is free for the following people:^[176]

• children aged six months to five years;
• people aged 65 years and over;
• Aboriginal and Torres Strait Islander people
  aged six months and over;
• pregnant women; and
• anyone over six months of age with medical conditions such as severe asthma, lung disease or heart disease, low immunity or diabetes that can lead to complications from influenza.

Uptake

At risk groups

Uptake of flu vaccination, both seasonally and during pandemics, is often low.^[178] Systematic reviews of pandemic flu vaccination uptake have identified several personal factors that may influence uptake, including gender (higher uptake in men), ethnicity (higher in people from ethnic minorities) and having a chronic illness.^[179][180] Beliefs in the safety and effectiveness of the vaccine are also important.^[178]

A number of measures have been found to be useful to increase rates of vaccination in those over sixty including: patient reminders using leaflets and letters, postcard reminders, client outreach programs, vaccine home visits, group vaccinations, free vaccinations, physician payment, physician reminders and encouraging physician competition.^[181]

Health care workers

Frontline health care workers are often recommended to get seasonal and any pandemic flu vaccination. For example, in the UK all health care workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the

The main reason to vaccinate health care workers is to prevent staff from spreading flu to their patients and to reduce staff absence at a time of high service demand, but the reasons health care workers state for their decisions to accept or decline vaccination may more often be to do with perceived personal benefits.[150]

In Victoria (Australia) public hospitals, rates of health care worker vaccination in 2005 ranged from 34% for non-clinical staff to 42% for laboratory staff. One of the reasons for rejecting vaccines was concern over adverse reactions; in one study, 31% of resident physicians at a teaching hospital incorrectly believed Australian vaccines could cause influenza.^[189]

Manufacturing

Research continues into the idea of a "universal" influenza vaccine that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses.^[190] No vaccine candidates had been announced by November 2007,^[191] but as of 2021^[update], there are several universal vaccines candidates, in pre-clinical development and in clinical trials.^{[192][193][194][195]}

In a 2007 report, the global capacity of approximately 826 million seasonal influenza vaccine doses (inactivated and live) was double the production of 413 million doses. In an aggressive scenario of producing

Most flu vaccines are grown by vaccine manufacturers in fertilized chicken eggs.^[197][191] In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season.^[197][198] Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs are inoculated separately. These monovalent harvests are then combined to make the trivalent vaccine.^[199]

As of November 2007^[update], both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union also approved

Influenza vaccines are produced in pathogen-free eggs that are eleven or twelve days old.^[200] The top of the egg is disinfected by wiping it with alcohol and then the egg is candled to identify a non-veinous area in the allantoic cavity where a small hole is poked to serve as a pressure release.^[201] A second hole is made at the top of the egg, where the influenza virus is injected in the allantoic cavity, past the chorioallantoic membrane. The two holes are then sealed with melted paraffin and the inoculated eggs are incubated for 48 hours at 37 degrees Celsius.^[200] During incubation time, the virus replicates and newly replicated viruses are released into the allantoic fluid^[202]

After the 48-hour incubation period, the top of the egg is cracked and the ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers.^[202] Up to 3 eggs are needed to produce one dose of a trivalent vaccine, and an estimated 600 million eggs are produced each year for flu vaccine production.^[203]

Other methods of manufacture

Methods of vaccine generation that bypass the need for eggs include the construction of influenza

A gene-based DNA vaccine, used to prime the immune system after boosting with an inactivated H5N1 vaccine, underwent clinical trials in 2011.^{[205][206][207]}

On November 20, 2012, Novartis received FDA approval for the first cell-culture vaccine.^{[139][32][208][209]} In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States.^{[34][210][211][212]}

On September 17, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture).^[213] The applicant for this medicinal product is Sanofi Pasteur.^[213] Supemtek was approved for medical use in the European Union in November 2020.^[140][214]

Australia authorised its first and cell-based vaccine in March 2021, based on an "eternal cell line" of a dog kidney. Because of the way it is produced, it produces better-matched vaccine (to the flu strains).^[135]

Vaccine manufacturing countries

According to the WHO, as of 2019^[update], countries where influenza vaccine is produced include:^[215]

In addition, Kazakhstan, Serbia and Thailand had facilities in final stages of establishing production.^[215]

Cost-effectiveness

The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings.^[216] In the elderly (over 65), the majority of published studies have found that vaccination is cost saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination.^[217] In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however the results of these studies were often found to be dependent on key assumptions used in the economic evaluations.^[218] The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden,^[219] as well as the seasonal variability in the circulating strains and the match of the vaccine.^[220][221] In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits.^[222] In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings.^[223] Several studies have attempted to predict the cost-effectiveness of interventions (including prepandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it.^[224]

Research

The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles).^[228] As of July 2009^[update], more than seventy known clinical trials have been completed or are ongoing for pandemic influenza vaccines.^[229] In September 2009, the FDA approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month.^[230]

In January 2020, the US Food and Drug Administration (FDA) approved Audenz as a vaccine for the H5N1 flu virus.^[231] Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine.^[232]

Universal flu vaccines

A

The challenges for researchers are to identify single antibodies that could neutralize many subtypes of the virus, so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift.^[233]

Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented different ways (as

An influenza vaccine and a COVID-19 vaccine may be given safely at the same time.^[57][242] Preliminary research indicates that influenza vaccination does not prevent COVID-19, but may reduce the incidence and severity of COVID-19 infection.^[243]

Criticism

Michael Osterholm, who led the Center for Infectious Disease Research and Policy 2012 review on flu vaccines, recommended getting the vaccine but criticized its promotion, saying, "We have overpromoted and overhyped this vaccine ... it does not protect as promoted. It's all a sales job: it's all public relations."^[245]

Veterinary use

Veterinary influenza vaccination aims to achieve the following four objectives:^[246]

1. Protection from clinical disease
2. Protection from infection with virulent virus
3. Protection from virus excretion
4. Serological differentiation of infected from vaccinated animals (so-called DIVA principle).

Horses

It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the International Federation for Equestrian Sports (FEI) requires vaccination every six months.^[248][249]

Poultry

A filtered and purified Influenza A vaccine for humans is being developed^[when?] and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu.^[253]

Pigs

Swine influenza has been recognized as a major problem since the outbreak in 1976. Evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection. Customised (autogenous) vaccines made from the specific viruses isolated, are made and used in the more difficult cases.^[254] The vaccine manufacturer Novartis claims that the H3N2 strain (first identified in 1998) has brought major losses to pig farmers. Abortion storms are a common sign and sows stop eating for a few days and run a high fever. The mortality rate can be as high as fifteen percent.^[255]

Dogs

In 2004, influenza A virus subtype H3N8 was discovered to cause canine influenza. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004.^[256]

Annual reformulation

Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance and Response System.^[257] The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Starting with the 2012–2013 Northern Hemisphere influenza season (coincident with the approval of quadrivalent influenza vaccines), the WHO has also recommended a 2nd B-strain for use in quadrivalent vaccines. The World Health Organization (WHO) coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year.

"The WHO Global Influenza Surveillance Network was established in 1952 [renamed "Global Influenza Surveillance and Response System" in 2011].^[258] The network comprises four WHO Collaborating Centres (WHO CCs) and 112 institutions in 83 countries, which are recognized by WHO as WHO National Influenza Centres (NICs). These NICs collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year."^[259]

The Global Influenza Surveillance and Response System's selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will predominate the next year, amounting in the end to well-informed but fallible guesswork.^[260]

Formal WHO recommendations were first issued in 1973. Beginning in 1999 there have been two recommendations per year: one for the northern hemisphere and the other for the southern hemisphere.^[261]

For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines.^[55]

Notes

References

Further reading

• The immunological basis for immunization series: module 23: influenza vaccines.
  ISBN 978-92-4-151305-0
  .
• Ramsay M, ed. (January 21, 2021). "Chapter 19: Influenza". Immunisation against infectious disease. Public Health England. Archived from the original on November 12, 2019. Retrieved October 24, 2019.
• Hall E, Wodi AP, Hamborsky J, Morelli V, Schillie S, eds. (2021). "Chapter 12: Influenza". Epidemiology and Prevention of Vaccine-Preventable Diseases (14th ed.). Washington D.C.: U.S. Centers for Disease Control and Prevention (CDC). Archived from the original on December 30, 2016. Retrieved October 24, 2019.
• Budd A, Blanton L, Grohskopf L, Campbell A, Dugan V, Wentworth DE, et al. (March 29, 2019). "Chapter 6: Influenza". In Roush SW, Baldy LM, Hall MA (eds.). Manual for the surveillance of vaccine-preventable diseases. Atlanta GA: U.S. Centers for Disease Control and Prevention (CDC). Archived from the original on August 1, 2020. Retrieved October 24, 2019.
• National Advisory Committee on Immunization (May 2020). "Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2020–2021" (PDF). Public Health Agency of Canada. Cat.: HP37-25F-PDF; Pub.: 200003. Archived (PDF) from the original on August 3, 2020. Retrieved June 2, 2020.
  • Lay summary in: Young K, Gemmill I, Harrison R, et al. (National Advisory Committee on Immunization) (May 7, 2020). "Summary of the NACI Seasonal Influenza Vaccine Statement for 2020–2021". Canada Communicable Disease Report. Vol. 46, no. 5.
• National Advisory Committee on Immunization (NACI) (May 2018). NACI literature review on the comparative effectiveness and immunogenicity of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older (PDF). Government of Canada.
  ISBN 978-0-660-26438-7. Cat.: HP40-213/2018E-PDF; Pub.: 180039. Archived
  (PDF) from the original on July 18, 2020. Retrieved January 12, 2020.
  • Lay summary in: Gemmill I, Young K, et al. (National Advisory Committee on Immunization) (June 7, 2018). "Summary of the NACI literature review on the comparative effectiveness of subunit and split virus inactivated influenza vaccines in older adults". Canada Communicable Disease Report. Vol. 44, no. 6.
• Rajaram S, Wojcik R, Moore C, Ortiz de Lejarazu R, de Lusignan S, Montomoli E, et al. (August 2020). "The impact of candidate influenza virus and egg-based manufacture on vaccine effectiveness: Literature review and expert consensus". Vaccine. 38 (38): 6047–6056.
  PMID 32600916
  .

External links

Wikiquote has quotations related to Influenza vaccine.

• Inactivated Influenza Vaccine Information Statement, US Centers for Disease Control and Prevention (CDC)
• Live, Intranasal Influenza Vaccine Information Statement, US Centers for Disease Control and Prevention (CDC)
• Seasonal Influenza (Flu) Vaccination and Preventable Disease, US Centers for Disease Control and Prevention (CDC)
• Misconceptions about Seasonal Flu and Flu Vaccines, US Centers for Disease Control and Prevention (CDC)
• Influenza Vaccines at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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